This monograph describes the progress in neuropathological HD research made during the last century, the neuropathological hallmarks of HD and their pathogenic relevance. Starting with the initial descriptions of the progressive degeneration of the striatum as one of the key events in HD, the worldwide practiced Vonsattel HD grading system of striatal neurodegeneration will be outlined. Correlating neuropathological data with results on the functional neuroanatomy of the human brain, subsequent chapters will highlight recent HD findings: the neuronal loss in the cerebral neo-and allocortex, the neurodegeneration of select thalamic nuclei, the affection of the cerebellar cortex and nuclei, the involvement of select brainstem nuclei, as well as the pathophysiological relevance of these pathologies for the clinical picture of HD. Finally, the potential pathophysiological role of neuronal huntingtin aggregations and the most important and enduring challenges of neuropathological HD research are discussed.

1. Introduction.- 2. The neuropathological grading of Huntington disease.- 3. The cerebral cortex in Huntingtons disease.- 4. Degeneration of select motor and limbic nuclei of the thalamus in Huntingtons disease.- 5. Consistent and widespread degeneration of the cerebellum in Huntingtons disease.- 6. Elucidation of the role of the premotor oculomotor brainstem nuclei in the pathogenesis of oculomotor dysfunctions in Huntingtons disease.- 7. Widespread brainstem neurodegeneration in Huntingtons disease.- 8. Intraneuronal transport and defense mechanisms with possible pathogenetic relevance in Huntingtons disease.- 9. The disease protein huntingtin and neuronal protein aggregations in Huntingtons disease.- 10. Pathological nerve cell alterations in Huntingtons disease (HD) and their possible role for the demise of nerve cells.- 11. Conclusions and outlook.